La Toxicité des glucocorticoïdes

par Fatemeh Valamanesh

Thèse de doctorat en Biologie

Sous la direction de Francine Béhar-Cohen et de Jean-François Zagury.

Soutenue en 2009

à Paris, CNAM .

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  • Titre traduit

    The Retinal toxicity of glucocorticoïdes

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  • Résumé

    Intravitreal injection of Kenacort Retard ® (Triamcinolone Acetonide (TA)) is widely used for the treatment of macular edema. Its anatomical efficiency is not always correlated to the functional improvement. The objective of my work was to look for potential retinal toxicity of glucocorticoïdes (GC). Intravitreal injection of clinical doses of TA induced histological lesions of the Retinal Pigmented Epithelium (RPE) and Retinal Müller Gliales cells (RMG), within one month. In vitro, a significant and dose dependent toxicity was induced by different GC formulations. The chemical properties of the GCs determine their toxicity; more hydrophobic compounds induce a more toxic effect. TA induces a non-apoptotic cell death through a mechanism related mainly to paraptosis for these two cell types. After intravitreal injection of Kenacort to the rat’s eye, we also observed a reduction of thickness of the choriocapillary and confirmed a significant rarefaction of this vascular network. TA induced direct retinal endothelial cells toxicity through caspase independent apoptotic pathways involving LEI/ L-DNase II and AIF. The expression of the VEGF induced by the specific RPE cells phagocytosis is not modified by TA suggesting that TA causes an indirect effect on the choriocapillary. Our results show that the GC induces cell death by non-classical pathways, explaining that although their toxicity is known, it was not evident to reveal it in different tissues. It is necessary to verify by specific methods the potential toxicity of TA used in clinical practice.

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  • Détails : 1 vol. (132 p.)
  • Annexes : Bibliogr. p. 115-135

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